The most common of the diseases characterized by acute and chronic inflammation of the joints is rheumatoid arthritis. As regards its etiology, none of the hypotheses proposed over time has ever found persuasive confirmation. Recently the etiopathogenetic hypothesis according to which the disease can be ascribed to the group of forms of hypersensitivity (the immune theory) has won the greatest agreement.
In the therapy of this disease, pharmaceuticals of various types are used with the object of controlling the inflammatory process and also to remedy the damage that the inflammatory process itself caused to the osteocartilaginous structures. Among these we have gold salts, antimalarials, penicillamine, and furthermore all the analgesic and steroid and nonsteroid anti-inflammatory pharmaceuticals. In particular, the symptomatic therapy is carried out by resorting to antiphlogistic drugs (nonsteroidal anti-inflammatory agents and cortisone compounds) and the base therapy using synthesized antimalarials, penicillamine, azathioprine, cyclophosphamide, gold salts, etc.
All these therapies, however, along with undoubtedly beneficial effects, create, to different degrees, undesired side effects. Such effects become more evident in all those forms which, like rheumatoid arthritis, require continuous therapy. In these degenerative inflammatory pathologies which, in the majority of cases, have a chronic course, the importance of finding an efficient pharmaceutical with scarce or no side effects is particularly felt.
Melatonin (N-acetyl-5-methoxytryptamine) is synthesized in the pineal body. It is derived from the hydroxylation and decarboxylation of tryptophan to 5-hydroxytryptamine (serotonin), and from the successive N-acetylation of the serotonin carried out by the enzyme N-acetyltransferase.
Melatonin is secreted rhythmically into the blood stream and distributed to the target cells to which it binds by means of specific binding sites. The circadian rhythm of melatonin levels is synchronized with light-dark alternation.
The activity of the N-acetyltransferase enzyme increases by 30 to 70 times during nighttime hours, and, consequently, melatonin reaches its maximum level between 24.00 and 04.00 h.
The synthesis of melatonin is promoted by noradrenergic stimulation by post-ganglionic sympathetic fibers which, at least in rodents terminate on beta-1 receptors.
Melatonin is metabolized in the brain and liver and is excreted in the urine. It functions as a neurotransmitter and neuromodulator and has a role of primary importance in the interaction of the neuroendocrine and immune systems.
No toxic effect following administration of melatonin has ever been recorded and, therefore, no contraindications exist for its use in human therapy.
Numerous studies have been conducted, also on healthy volunteers, to evaluate melatonin's effect as a synchronizer of sleep-wake rhythm.
Therapy with melatonin has been experimented in numerous and different pathological conditions, also at extremely high dosages. For example in Parkinson's disease, daily doses of melatonin of 6 gr. have been used without any damage, although without any demonstrable. advantages.
Many clinical and experimental observations have suggested the existence of a relationship between the pineal body and neoplastic diseases and, more particularly, have shown an anti-proliferative activity of melatonin.